Vascular endothelial growth factor (VEGF), a signaling molecule involved in angiogenesis, plays an important role in neuroprotection and neurogenesis. In the present study, we aimed to elucidate the mechanisms underlying endogenous acetylcholine (ACh)-induced VEGF expression in neurons and astrocytes, and identify the neuronal cells contributing to its expression in the medial septal area, a nuclear origin of cholinergic neurons mainly projecting to the hippocampus. The mRNA expression and secretion of VEGF were measured by RT-PCR and ELISA using mouse primary cultured cortical neurons and astrocytes. VEGF expression in the medial septal area was assessed by RT-PCR and immunostaining using mice treated with tacrine [9-amino-1,2,3,4-tetrahydro-acridine HCl (THA); 2.5 mg/kg, i.p.] once daily for 7 days. The THA treatment increased VEGF mRNA expression in neurons in a manner that was reversed by mecamylamine, a nicotinic ACh receptor (AChR) antagonist, whereas in mouse primary cultured astrocytes, carbachol, but not THA dose-dependently increased VEGF mRNA expression and secretion in a manner that was inhibited by scopolamine, a muscarinic AChR inhibitor. In in vivo studies, the administration of THA significantly increased the expression of VEGF in medial septal cholinergic neurons and the effects of THA were significantly blocked by mecamylamine. THA also significantly increased the expression levels of a phosphorylated form of VEGF receptor 2 (p-VEGFR2), an activated form of VEGFR2. The present results suggest that endogenous ACh plays an up-regulatory role for VEGF expression in neurons and astrocytes via different mechanisms. Moreover, endogenous ACh-induced increases in VEGF levels appear to activate VEGFR2 on medial septal cholinergic neurons via an autocrine mechanism.

血管内皮生长因子（VEGF），一种参与血管生成的信号分子，在神经保护和神经发生中起重要作用。在本研究中，我们旨在阐明内源性乙酰胆碱（ACh）诱导的神经元和星形胶质细胞VEGF表达的潜在机制，并鉴定有助于其在内侧中隔区表达的神经元细胞，该区域是胆碱能神经元的核主要起源于海马。使用小鼠原代培养的皮层神经元和星形胶质细胞通过RT-PCR和ELISA检测VEGF的mRNA表达和分泌。通过RT-PCR和使用他克林[9-氨基-1,2,3,4-四氢-啶盐酸盐（THA）处理的小鼠进行免疫染色，评估中隔区的VEGF表达。2.5 mg / kg，ip]，每天一次，共7天。THA处理增加了神经元中VEGF mRNA的表达，但被烟酰胺ACh受体（AChR）拮抗剂美卡敏逆转了，而在小鼠原代培养的星形胶质细胞中，卡巴胆碱（而不是THA）剂量依赖性地增加了神经元中VEGF mRNA的表达和分泌。被毒蕈碱型AChR抑制剂东pol碱抑制的方式。在在体内研究中，THA的给药显着增加了中隔间隔胆碱能神经元中VEGF的表达，而美卡明明显阻断了THA的作用。THA还显着提高了VEGF受体2的磷酸化形式（p-VEGFR2）（VEGFR2的激活形式）的表达水平。目前的结果表明内源性乙酰胆碱通过不同的机制在神经元和星形胶质细胞的VEGF表达中起上调作用。此外，内源性ACh诱导的VEGF水平升高似乎通过自分泌机制激活了中隔中间隔胆碱能神经元上的VEGFR2。